Dendritic cells (DCs) are presenting cells that stimulate strong B cell and T cell immunity in a large number of experimental systems, including CTL responses in vivo, but DCs are also known to be an important site for HIV-1 replication in patients. Aims 1 and 2 will dissect in dendritic cells innate susceptibility mechanisms. Several genetic subtypes of HIV-1 will be tested to see if DCs exhibit greater resistance to some e.g. to clade B vs. E. The investigators recently found that certain DCs are unusually permissive to HIV-1 entry by a CD4-dependent pathway, and this will be dissected at the level of chemokine and multilectin receptors. Aim 3 will approach neutralizing antibodies. New and existing antibodies will be tested for the capacity to bloc DC-mediated infections of human cells in vitro. High resolution SEM (with Erlandsen, U.MN) will be used to map neutralization epitopes on DCs. These aims can pursue DCs as natural sites for HIV-1 pathogenesis and protection in vivo, and thereby improve vaccine design.